DESCRIPTION:(Adapted from the Applicant's abstract) The purpose of this proposal is the discovery of novel agents for the treatment of AIDS-associated opportunistic mycobacterial infections. The hypothesis is that new drugs can achieve improved entry into mycobacteria and enhanced activity against these pathogens by augmentation of drug lipophilicity. The proposal has three specific aims: 1) Prepare novel agents using methods of synthetic organic chemistry, 2) Evaluate the new drug candidates by testing against both susceptible and drug-resistant strains of Mycobacterium tuberculosis, and 3) Develop a robust analytical method (near-infrared spectroscopy) to monitor conveniently and rapidly the chemical synthesis of the new compounds. The project is designed to allow feedback from the microbiological testing to guide new synthesis.